Worms in the gut keep mice from getting plump on high-fat food

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The intestinal parasites also changed how food affected their host's immune system

FAITH RUDEBUSCH JUN 13, 2018 — 6:45 AM EST

This round worm, Heligmosomoides polygyrus, was retrieved from the gut of a wood mouse. New research shows that being infected by such parasites can keep animals from gaining weight, even when eating fattening food.

NALDO-CROCODUCK/WIKIMEDIA COMMONS (CC BY-SA 3.0)

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As a man walks barefoot outdoors, unknowingly his feet encounter very tiny worms. Secretly, one or more of the parasites crawl onto his skin — and then through it. Once inside, these hookworms move around until they end up in their victim’s gut. They latch onto their host’s intestines and from there feast on his blood.

This is not the script for some horror movie. It’s what has already happened to roughly one in every four people on Earth. That’s some 1.9 billion people. But a new study in rodents suggests that hosting these hookworms may have some upsides: weight control and a healthier immune system.

Let’s not downplay the fact that hookworms can bring misery. They eat some of their hosts’ blood, leaving them with lower levels of iron. This may make it hard for the bloodstream to carry a normal load of oxygen through the body, a condition known as anemia (Uh-NEE-mee-uh). The worms also can cause painful rashes and stunt a child’s growth and development. Few doctors, then, would ever prescribe the worms to their patients. But the new data do point to how mammals may have evolved to deal with — indeed, accommodate — some common, nasty infections. And people have had a long time to deal with hookworms. Even ancient mummies show signs of being infected.

During the last century, though, hookworm infections have become rare in developed countries, such as the United States.

In countries that are not so industrialized, “there are lots of infectious diseases, including worm infections,” notes Haining Shi. He studies diseases in children at Harvard Medical School in Boston, Mass. People who live in such countries, he adds, also have lower rates of certain chronic (long-term) diseases than do folks in industrial nations. This prompted Shi’s team to test an idea: Might parasites help prevent some serious, chronic ailments?

Explainer: All about the calorie

The group decided to focus on obesity. One third of U.S. adults are obese. Nearly one in every six children also are overweight or obese. Carrying too much body fat can lead to a host of other serious health problems, including heart disease and type 2 diabetes.

Obesity comes from consuming more energy, in the form of food, than the body uses. But not all bodies use energy with the same efficiency. And Shi’s team now shows that parasitic worms change how efficiently a body uses energy — at least in mice.

How they found this out

The researchers chose mice as a model for what might be expected to occur in people. Like people, mice that eat high-fat foods tend to get fat. These animals also can host parasitic worms. The parasite that Shi chose to work with, Heligmosomoides polygyrus (Heh-LIG-moh-soh-MOY-ih-dees Pah-lee-GY-rus), is not a hookworm. And it does not live in people. But hookworms are a type of nematode (NEE-muh-toad). And this worm is a nematode similar to the hookworms that infect people.

The scientists divided mice into four groups. Two groups were fed a normal diet. The rest ate high-fat chow. The researchers infected one group of mice on each of the two diets with nematode larvae. Shi’s group then measured the animals’ growth for up to 105 days.

The noninfected mice eating the high-fat food nearly doubled in size. But they were the only group to do so. All animals on the regular food grew at the normal rate. So did worm-infected mice eating the high-fat food.

The right mouse has worms in its gut and gained less weight than non-wormy mice eating the same high-fat food.

Chienwen Su

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If the weight loss happened because infected mice were losing blood to the worms, why didn’t those on a normal diet lose weight compared to the uninfected mice? The answer, Shi’s group showed, was a bit complicated. The worms changed how the infected mice processed high-fat meals.

When uninfected mice fattened up, their blood sugar rose. So did blood levels of fatty materials, such as cholesterol (Koh-LES-tur-awl) and triglycerides (Try-GLIH-sur-eydz). Even their livers got fattier. And that wasn’t all. Different fat-related genes turned on in these animals.

No mouse eating a normal diet showed such changes. Neither did the worm-infected mice eating high fat meals.

Worms even affected what type of fat was stored. Like humans, mice have two types. White fat is an energy-rich type that can be burned at some future date. Think of it as fuel stored in the body’s pantries. Brown fat is enriched with a special molecule known as an uncoupling protein. This protein turns on the body’s energy-burning machinery.

The obese mice had mostly white fat. Wormy rodents that ate the high-fat diet had bonus brown fat.

Indeed, Shi now reports, “We found that the worm has a beneficial effect” — especially in mice eating a fatty diet. His team published its results online March 15 in Scientific Reports.

What was behind all of these changes?

How could worms alter blood, livers, gene activity and brown-fat levels? Shi now suspects that cells in the immune system drove these changes.

Other studies had shown that parasitic worms can act on several specific cells. Shi tested one type of immune cell known as a macrophage (MAK-roh-fayj).

These are big cells. They eat viruses and bacteria — germs that can make a person sick. They also can trigger inflammation. You may have noticed one type of inflammation in your own body. When a cut or scrape becomes infected, it becomes red, swollen and hot. This inflammation is one way that the immune system fights infections. But chronic (long-term) inflammation is not healthy. And low-grade, long-term inflammation is seen in animals and people that are obese.

Animals get obese as they produce more white fat. This fat collects macrophages. There are different types. The M1 type triggers inflammation. M2 macrophages shut down inflammation. Fat mice without worms had more M1 macrophages. Wormy mice had more of the M2 type.

The researchers thought that the M2 macrophage might be the key to how worm infections altered the mice. To test this, they transferred macrophages from mice with and without the worms into noninfected obese mice.

These fat mice getting macrophages from mice without worms kept gaining a lot of weight. But those that got macrophages from worm-infected mice gained less. They also had healthier blood levels of sugar, fat and cholesterol. They even had more decoupling proteins in their fat, making it browner.

Shi’s team now concludes that hosting worms changed how mice processed high-fat diets just by changing their macrophages.

The researchers had previously shown that parasitic worms affect which microbes live in mouse guts (microbes live in all mammals’ guts). Other researchers found that worms protect mice from different diseases caused by a faulty immune system. Marc Hübner is one of these scientists.

Hübner studies how parasites affect diabetes. He works at the Institute for Medical Microbiology in Bonn, Germany. The Harvard team’s study confirms what scientists suspected about how worms change mice, he says. He adds that as such studies go, “this is a really good [one].”

Shi cautions that there are always two sides to a story. It’s good that worms can lower chronic inflammation. But what happens when someone with a parasite also encounters a germ that causes disease? Shi suspects that their immune system won’t be able to fight the new infection very well. Parasitic worms might therefore make other common infections more dangerous. This, he says, is a big problem for children with worms.

“In humans, we still have some work to do,” says Shi. “We see that the worm is really important and beneficial. But in reality … nobody will take a live worm.” He hopes to find out more about how worms change the immune system. Then, scientists may be able to figure out how to treat people in such a way that they get those benefits without having to become infected with the worms.

Power Words

anemia    A disease caused by not having enough red blood cells. This reduces the body’s ability to carry oxygen efficiently to all tissues.

bacteria    (singular: bacterium) Single-celled organisms. These dwell nearly everywhere on Earth, from the bottom of the sea to inside other living organisms (such as plants and animals).

blood sugar    The body circulates glucose, a type of simple sugar, in blood to tissues of the body where it will be used as a fuel. The body extracts this simple sugar from breakdown of sugars and starches. However, some diseases, most notably diabetes, can allow an unhealthy concentration of this sugar to build up in blood.

brown fat    A type of stored fat that the body burns when it senses a strong need to heat up the body (owing to being in a cold environment). It takes its name from the actual color of the fat, which is not light colored as the more common “white” body fat is. The storage of excess calories as this type of fat, and its later use by the body, are controlled by nervous system.

calorie    The amount of energy needed to raise the temperature of 1 gram of water by 1 degree Celsius. It is typically used as a measurement of the energy contained in some defined amount of food.

cell    The smallest structural and functional unit of an organism. Typically too small to see with the unaided eye, it consists of a watery fluid surrounded by a membrane or wall.

cholesterol    A fatty material in animals that forms a part of cell walls. In vertebrate animals, it travels through the blood in little vessels known as lipoproteins. Excessive levels in the blood can signal risks to blood vessels and heart.

chronic    A condition, such as an illness (or its symptoms, including pain), that lasts for a long time.

development    (in biology) The growth of an organism from conception through adulthood, often undergoing changes in chemistry, size and sometimes even shape. (in economics and social sciences) The conversion of land from its natural state into another so that it can be used for housing, agriculture, or resource development.

diabetes    A disease where the body either makes too little of the hormone insulin (known as type 1 disease) or ignores the presence of too much insulin when it is present (known as type 2 diabetes).

diet    The foods and liquids ingested by an animal to provide the nutrition it needs to grow and maintain health. (verb) To adopt a specific food-intake plan for the purpose of controlling body weight.

fat    A natural oily or greasy substance occurring in plants and in animal bodies, especially when deposited as a layer under the skin or around certain organs. Fat’s primary role is as an energy reserve. Fat also is a vital nutrient, though it can be harmful if consumed in excessive amounts.

fuel    Any material that will release energy during a controlled chemical or nuclear reaction. Fossil fuels (coal, natural gas and petroleum) are a common type that liberate their energy through chemical reactions that take place when heated (usually to the point of burning).

gene    (adj. genetic) A segment of DNA that codes, or holds instructions, for a cell’s production of a protein. Offspring inherit genes from their parents. Genes influence how an organism looks and behaves.

germ    Any one-celled microorganism, such as a bacterium or fungal species, or a virus particle. Some germs cause disease. Others can promote the health of more complex organisms, including birds and mammals. The health effects of most germs, however, remain unknown.

gut    An informal term for the gastrointestinal tract, especially the intestines.

hookworm    A type of bloodsucking nematode (small worm) that lives within the intestines of people and other animals. With hooklike mouthparts, it attaches to the wall of the gut. This parasite punctures blood vessels there to reach the blood it seeks. 

host      (in biology and medicine) The organism (or environment) in which some other thing resides. Humans may be a temporary host for food-poisoning germs or other infective agents.

immune    (adj.) Having to do with the immunity. (v.) Able to ward off a particular infection. Alternatively, this term can be used to mean an organism shows no impacts from exposure to a particular poison or process. More generally, the term may signal that something cannot be hurt by a particular drug, disease or chemical.

immune system     The collection of cells and their responses that help the body fight off infections and deal with foreign substances that may provoke allergies.

infect    To spread a disease from one organism to another. This usually involves introducing some sort of disease-causing germ or parasite to an individual.

infection    A disease that can spread from one organism to another. It’s usually caused by some type of germ.

inflammation    (adj. inflammatory) The body’s response to cellular injury and obesity; it often involves swelling, redness, heat and pain. It also is an underlying feature responsible for the development and aggravation of many diseases, especially heart disease and diabetes.

iron    A metallic element that is common within minerals in Earth’s crust and in its hot core. This metal also is found in cosmic dust and in many meteorites.

larvae    (plural: larvae) An immature life stage of an insect, which often has a distinctly different form as an adult. (Sometimes used to describe such a stage in the development of fish, frogs and other animals.)

liver    An organ of the body of animals with backbones that performs a number of important functions. It can store fat and sugar as energy, break down harmful substances for excretion by the body, and secrete bile, a greenish fluid released into the gut, where it helps digest fats and neutralize acids.

macrophage    A type of white blood cell dispatched by the immune system. Like janitors of the body, they gobble up germs, wastes and debris for disposal. These cells also stimulate other immune cells by exposing them to small bits of the invaders.

mammal    A warm-blooded animal distinguished by the possession of hair or fur, the secretion of milk by females for feeding their young, and (typically) the bearing of live young.

microbe    Short for microorganism. A living thing that is too small to see with the unaided eye, including bacteria, some fungi and many other organisms such as amoebas. Most consist of a single cell.

microbiology    The study of microbes, principally bacteria, fungi and viruses. Scientists who study microbes and the infections they can cause or ways that they can interact with their environment are known as microbiologists.

model    A simulation of a real-world event (usually using a computer) that has been developed to predict one or more likely outcomes. Or an individual that is meant to display how something would work in or look on others.

molecule    An electrically neutral group of atoms that represents the smallest possible amount of a chemical compound. Molecules can be made of single types of atoms or of different types. For example, the oxygen in the air is made of two oxygen atoms (O2), but water is made of two hydrogen atoms and one oxygen atom (H2O).

nematode    A type of roundworm, usually found in soil, that also can live within other creatures as a parasite. It is usually quite small, with no eyes, ears or nose. However, the occasional species can grow up to a meter long.

obesity    (adj. obese) Extreme overweight. Obesity is associated with a wide range of health problems, including type 2 diabetes and high blood pressure.

overweight    A medical condition where the body has accumulated too much body fat. People are not considered overweight if they weigh more than is normal for their age and height, but that extra weight comes from bone or muscle.

oxygen    A gas that makes up about 21 percent of Earth's atmosphere. All animals and many microorganisms need oxygen to fuel their growth (and metabolism).

parasite    An organism that gets benefits from another species, called a host, but doesn’t provide that host any benefits. Classic examples of parasites include ticks, fleas and tapeworms.

protein    A compound made from one or more long chains of amino acids. Proteins are an essential part of all living organisms. They form the basis of living cells, muscle and tissues; they also do the work inside of cells. Among the better-known, stand-alone proteins are the hemoglobin (in blood) and the antibodies (also in blood) that attempt to fight infections. Medicines frequently work by latching onto proteins.

rodent    A mammal of the order Rodentia, a group that includes mice, rats, squirrels, guinea pigs, hamsters and porcupines.

triglyceride    The main ingredient in many animal fats and oils. A high level of triglycerides in the blood puts a person at risk for heart disease or stroke.